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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Selective Inhibition of Deamidated Triosephosphate Isomerase by Disulfiram, Curcumin, and Sodium Dichloroacetate: Synergistic Therapeutic Strategies for T-Cell Acute Lymphoblastic Leukemia in Jurkat Cells

by
Luis A. Flores-López
1,*,
Ignacio De la Mora-De la Mora
2,
Claudia M. Malagón-Reyes
3,
Itzhel García-Torres
2,
Yoalli Martínez-Pérez
4,
Gabriela López-Herrera
5,
Gloria Hernández-Alcántara
6,
Gloria León-Avila
7,
Gabriel López-Velázquez
2,
Alberto Olaya-Vargas
8,
Saúl Gómez-Manzo
9 and
Sergio Enríquez-Flores
2,*
1
Laboratorio de Biomoléculas y Salud Infantil, CONAHCYT-Instituto Nacional de Pediatría, Mexico City 04530, Mexico
2
Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Mexico City 04530, Mexico
3
Posgrado en Ciencias Biológicas, (Maestría), Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
4
Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Ciudad de México, Mexico City 14380, Mexico
5
Laboratorio de Inmunodeficiencias, Instituto Nacional de Pediatría, Mexico City 04530, Mexico
6
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apartado Postal 70-159, Mexico City 04510, Mexico
7
Departamento de Zoología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Casco de Santo Tomás, Ciudad de México 11340, Mexico
8
Trasplante de Células Madre y Terapia Celular, Instituto Nacional de Pediatría, Mexico City 04530, Mexico
9
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Mexico City 04530, Mexico
*
Authors to whom correspondence should be addressed.
Biomolecules 2024, 14(10), 1295; https://doi.org/10.3390/biom14101295 (registering DOI)
Submission received: 27 August 2024 / Revised: 9 October 2024 / Accepted: 10 October 2024 / Published: 13 October 2024
(This article belongs to the Section Enzymology)
Review Reports Versions Notes

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy.
Keywords: cancer; leukemia; glycolysis; TPI; repurposing drugs cancer; leukemia; glycolysis; TPI; repurposing drugs

Share and Cite

MDPI and ACS Style

Flores-López, L.A.; De la Mora-De la Mora, I.; Malagón-Reyes, C.M.; García-Torres, I.; Martínez-Pérez, Y.; López-Herrera, G.; Hernández-Alcántara, G.; León-Avila, G.; López-Velázquez, G.; Olaya-Vargas, A.; et al. Selective Inhibition of Deamidated Triosephosphate Isomerase by Disulfiram, Curcumin, and Sodium Dichloroacetate: Synergistic Therapeutic Strategies for T-Cell Acute Lymphoblastic Leukemia in Jurkat Cells. Biomolecules 2024, 14, 1295. https://doi.org/10.3390/biom14101295

AMA Style

Flores-López LA, De la Mora-De la Mora I, Malagón-Reyes CM, García-Torres I, Martínez-Pérez Y, López-Herrera G, Hernández-Alcántara G, León-Avila G, López-Velázquez G, Olaya-Vargas A, et al. Selective Inhibition of Deamidated Triosephosphate Isomerase by Disulfiram, Curcumin, and Sodium Dichloroacetate: Synergistic Therapeutic Strategies for T-Cell Acute Lymphoblastic Leukemia in Jurkat Cells. Biomolecules. 2024; 14(10):1295. https://doi.org/10.3390/biom14101295

Chicago/Turabian Style

Flores-López, Luis A., Ignacio De la Mora-De la Mora, Claudia M. Malagón-Reyes, Itzhel García-Torres, Yoalli Martínez-Pérez, Gabriela López-Herrera, Gloria Hernández-Alcántara, Gloria León-Avila, Gabriel López-Velázquez, Alberto Olaya-Vargas, and et al. 2024. "Selective Inhibition of Deamidated Triosephosphate Isomerase by Disulfiram, Curcumin, and Sodium Dichloroacetate: Synergistic Therapeutic Strategies for T-Cell Acute Lymphoblastic Leukemia in Jurkat Cells" Biomolecules 14, no. 10: 1295. https://doi.org/10.3390/biom14101295

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